1. Field of the Invention
The present invention relates to an agent for improving hemodynamics. The present invention also relates to methods for improving hemodynamics.
2. Discussion of the Background
With the westernization of lifestyle in recent years, diseases such as angina pectoris, myocardial infarction, cerebral infarction and the like, along with cancer, have become the primary cause of deaths of Japanese people. In addition, complications developed with the progression of diabetes, such as nephropathy, retinopathy and the like, increase kidney dialysis and bedridden patients, forming a biggest cause straining the medical expenses. All of these are diseases in the blood vascular system, which are extremely difficult to cure after onset and significantly degrade the QOL (quality of life) of patients. Therefore, an arrangement to always keep damage to blood vessels and the level of aging within appropriate ranges is extremely important also from social aspects.
As risk factors that damage blood vessels and accelerate aging, hyperlipidemia, hyperglycemia, hypertension, obesity and the like are conventionally known. High blood lipid, blood glucose, blood pressure and the like are known to reduce the extensibility of blood vascular walls and change reactivity with various vascular tonus regulatory factors such as nitric oxide (NO) and angiotensin II. Therefore, control of these risk factors to appropriate levels is important, and drugs, food and the like for this object have been continuously developed. Even when the levels of these risk factors are the same, the damage to and aging of blood vessels are interindividually different and cannot be consistent. Therefore, direct measurement of the level of aging of blood vessels becomes important. Recently, it is becoming possible to noninvasively and quantitatively evaluate the aging level of blood vessels by measuring and analyzing changes in the arterial blood pressure due to heartbeat, i.e., pulse wave. In as much as pulse wave velocity (PWV) showing the velocity of the pulse wave along an artery, Augmentation Index (AIx) reflecting the total peripheral vascular resistance, particular wave form component of second derivative of photoplethysmogram, which is the laplacian of the digital plethysmogram finger plethysmogram, as well as a numerical index consisting thereof and the like show certain changes with aging (Schiffrin, Am. J. Hypertens., 17: 395, 2004, and Takazawa, et. al., Hypertension, 32:365, 1998), the concept of “vascular age” based on the standard value for each age is prevailing.
In recent clinical tests, moreover, the number of reports showing the usefulness of PWV, AIx and the like as risk prediction factors of cardiovascular diseases is increasing (Boutuyrie, et. al., Hypertension, 39:10, 2002, and London, et. al., Hypertension, 38:434, 2001). While these indices are considered to mainly reflect extensibility, wall thickness and vascular resistance of blood vascular walls, it is clear that they are not defined only by blood pressure or mere structural stiffness, in view of the reports documenting examples showing that PWV changes differently even when the level of hypotensive effect is the same (Asmar, et. al., J. Hypertens., 19:813, 2001), and that these indices are improved by a light exercise therapy (Sugawara et al., abstract of the third meeting of Clinical Arterial Wave Society, 39, 2003) or a short-term intervention of a certain drug (Matsuo et al., abstract of the second meeting of Clinical Arterial Wave Society, 33, 2002, and Watanabe, et. al., American College of Cardiology 51 st Annual Scientific Session, 2002). Involvement of factors such as sympathetic nerve activity, vascular endothelial function, adiponectin and the like is also suggested (McVeigh, et. al., Arterioscler. Thromb. Vasc. Biol., 14: 1425, 1994, Agata, et. al., Circul. J., 68: 1194, 2004 and Akimoto et al., ‘Pulse wave velocity’, 104, MEDICA1 VIEW, 2002), and therefore, these indices are taken as indices of total risk for vascular walls including temporary functional vascular tone rather than mere indices of atherosclerosis.
Therefore, a component capable of directly improving a pulse wave-related index such as PWV, AIx and the like and maintaining the “vascular age” within an appropriate range is highly likely more useful for the prophylaxis or treatment of cardiovascular diseases than a component that indirectly decreases a blood vessel risk through improvement of classic indices such as blood cholesterol, blood pressure and the like. The number of reports relating to a PWV improving effect by a part of pharmaceutical products (statin, angiotensin II receptor blocker, EPA preparation and the like) is increasing in recent years (Agata, et al., Circul. J., 68:1194, 2004, Asmar, ‘Pulse wave velocity and therapy’, 142, Elsevier, 1999 and Sato, et al., J. Cardiovasc. Pharmacol., 22: 1, 1993). The report on a lower incidence of cardiovascular event in a group showing a good PWV improvement rate, though with a similar level of hypotensive action (Yamashina, Toyama, ‘Pulse wave velocity’, 120, MEDICA1 VIEW, 2002) is one such example. However, long-term consecutive use of these pharmaceutical products may cause adverse effects, and there have been found only a few food components considered to be safer and known to improve PWV, AIx, second derivative of photoplethysmogram waveform (Teede, et al., Arterioscler. Thromb. Vasc. Biol., 23: 1066, 2003 and Nestel, et al., Arterioscler. Thromb. Vasc. Biol., 17: 1163, 1997).
The composition for improvement of hemodynamics of the present invention, as mentioned below, suppresses an increase of the pulse wave velocity (PWV) and Augmentation Index (AIx) in rabbit, as well as decreases the blood pressure (systolic blood pressure, mean blood pressure) and pulse pressure. While these hemodynamic indices are known to increase as atherosclerosis progresses, it is known that they are also degraded by, in addition to structural stiffening of blood vessels, an increase in the total vascular resistance due to promoted functional vascular tone.